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Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 May 2026 | Viewed by 4018

Special Issue Editors


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Guest Editor
2nd Department of Urology Sismanoglio General Hospital, University of Athens, Athens, Greece
Interests: urology

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Guest Editor
2nd Department of Urology, National and Kapodistrian University of Athens, Sismanogleion Hospital, 11526 Athens, Greece
Interests: urolithiasis; robotic surgery; prostate cancer; kidney cancer; bladder cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will focus on recent innovations and clinical advances in prostate cancer, spanning early detection, risk stratification, novel imaging modalities, minimally invasive and robotic surgical techniques, and the integration of molecular biomarkers into personalized treatment strategies. Emphasis will be placed on multidisciplinary approaches and the evolving role of artificial intelligence and genomics in clinical decision making.

For this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Prostate cancer;
  • Precision medicine;
  • Molecular biomarkers;
  • Risk stratification;
  • Robotic surgery;
  • Artificial intelligence;
  • Genomics;
  • Personalized treatment;
  • Imaging modalities;
  • Multidisciplinary approach.

We look forward to receiving your contributions.

Dr. Stamatios N. Katsimperis
Dr. Lazaros Tzelves
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • precision medicine
  • molecular biomarkers
  • risk stratification
  • robotic surgery
  • artificial intelligence
  • genomics
  • personalized treatment
  • imaging modalities
  • multidisciplinary approach

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Published Papers (4 papers)

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Research

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33 pages, 2164 KB  
Article
Clinically Significant ISUP Upgrading in the Multiparametric MRI Era: Biopsy Tumor Burden Outperforms Complex Machine Learning Models in a Single-Center Exploratory Cohort
by Cristian Condoiu, Adelina Baloi, Dorel Sandesc, Alin Adrian Cumpanas, Silviu Latcu, Vlad Dema, Radu Caprariu, Alina Cristina Barb, Andreea Ciucurita, Adelina Marinescu, Talida Georgiana Cut and Razvan Bardan
Cancers 2026, 18(5), 730; https://doi.org/10.3390/cancers18050730 - 24 Feb 2026
Viewed by 533
Abstract
Background/Objectives: Despite multiparametric MRI (mpMRI)-guided biopsy, clinically significant upgrading (CSU) of ISUP Grade Group (GG) at radical prostatectomy (RP) remains common in prostate cancer (PCa). We aimed to identify predictors of CSU (biopsy GG ≤ 2 to RP GG ≥ 3) using [...] Read more.
Background/Objectives: Despite multiparametric MRI (mpMRI)-guided biopsy, clinically significant upgrading (CSU) of ISUP Grade Group (GG) at radical prostatectomy (RP) remains common in prostate cancer (PCa). We aimed to identify predictors of CSU (biopsy GG ≤ 2 to RP GG ≥ 3) using routine preoperative variables, and to benchmark a parsimonious logistic model against multiple machine learning (ML) classifiers. Methods: In this single-center exploratory analysis, 96 consecutive PCa patients underwent pre-biopsy mpMRI, systematic ± MRI-targeted biopsy, and RP. Predictive modeling was restricted to biopsy GG 1–2 patients (n = 64). LASSO-guided feature selection and Firth-penalized logistic regression were used to build a locked reference model, evaluated against ML classifiers using cross-validated discrimination, calibration, and decision curve analysis. Results: CSU occurred in 10/64 patients (15.6%). Positive core ratio was the dominant independent predictor (adjusted OR 1.54 per 10% increase, 95% CI 1.10–2.17). PSA density (PSAD) showed a consistent positive association but did not retain independent significance. The locked two-variable model (AUC ≈ 0.75–0.79) outperformed all ML classifiers in discrimination, calibration, and net clinical benefit; however, the limited event count (n = 10) constrains model stability, and these findings require external validation. Conclusions: In a PCa mpMRI-informed diagnostic pathway, CSU is primarily driven by biopsy tumor burden. A simple logistic model based on positive core ratio and PSAD outperformed more complex ML approaches in this exploratory cohort, supporting integration of biopsy tumor burden metrics into preoperative risk stratification pending external validation. Full article
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16 pages, 1199 KB  
Article
Neoadjuvant ADT for Asian Patients Undergoing Robotic Radical Prostatectomy Is the Conversation Over?—A Propensity-Matched Comparison
by John Joson Ng, Sean Lim, Alvin Lee, Yu Guang Tan, Kae Jack Tay, Henry Ho, John Yuen and Kenneth Chen
Cancers 2026, 18(4), 661; https://doi.org/10.3390/cancers18040661 - 18 Feb 2026
Viewed by 518
Abstract
Background: Evidence for neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) remains inconclusive, and current guidelines do not endorse its routine use. Objective: We aimed to evaluate the impact of neoadjuvant ADT on surgical and oncologic outcomes in a Singaporean cohort undergoing [...] Read more.
Background: Evidence for neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) remains inconclusive, and current guidelines do not endorse its routine use. Objective: We aimed to evaluate the impact of neoadjuvant ADT on surgical and oncologic outcomes in a Singaporean cohort undergoing radical prostatectomy. Design, setting, and participants: In this retrospective study, 1091 men underwent RP between 2013 and 2024; a total of 105 received neoadjuvant ADT and 986 did not. A 1:1 propensity score-matched analysis was performed on age, PSA, PSA density, Gleason score, clinical T-stage, and receipt of adjuvant therapies, yielding 105 matched pairs. Outcome measurements and statistical analysis: The primary outcome was biochemical recurrence (BCR). Secondary surgical outcomes included operative time, estimated blood loss, length of stay, catheter duration, and postoperative complications. Secondary oncologic outcomes included extracapsular extension, margin status, seminal vesicle invasion, lymph node involvement, clinical-to-pathological T-stage downstaging, Gleason score decrease, and PSA decrease. Kaplan–Meier survival and univariable linear and logistic regression analyses were used. Subgroup analysis was performed using stratified odds ratios to identify clinical subgroups that derived the greatest benefit from neoadjuvant ADT in terms of biochemical recurrence reduction. Results and limitations: After matching, neoadjuvant ADT was associated with a lower rate of extracapsular extension (30.8% vs. 51.4%, p = 0.004), positive surgical margins (18.4% vs. 39.4%, p = 0.002), lymph node involvement (1.0% vs. 13.0%, p = 0.002), and biochemical recurrence (4.8% vs. 18.1%, p = 0.005). There were no significant differences in operative time, blood loss, length of stay, or complication rates. Before matching, 2-year biochemical recurrence-free survival (BCR-FS) did not differ significantly (93.0% vs. 88.2%, log-rank p = 0.26), but after matching, BCR-FS favored ADT (93.0% vs. 81.8%, log-rank p = 0.02). Subgroup analysis showed that the reduction in biochemical recurrence with neoadjuvant ADT was more pronounced in patients with PSA density ≥ 0.20 ng/mL2, Gleason score ≥ 8, and clinical T3 disease. Limitations include the retrospective design and potential residual confounding. Conclusions: Neoadjuvant ADT prior to RP significantly reduces locoregional spread and biochemical recurrence without increasing perioperative morbidity. Prospective trials are needed to confirm its benefit in high-risk prostate cancer. Full article
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Review

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22 pages, 1518 KB  
Review
Adipokine Metabolic Drivers, Gut Dysbiosis, and the Prostate Microbiome: Novel Pathway Enrichment Analysis of the Adiposity-Based Chronic Disease—Prostate Cancer Network
by Zachary Dovey, Elena Tomas Bort and Jeffrey I. Mechanick
Cancers 2026, 18(2), 206; https://doi.org/10.3390/cancers18020206 - 8 Jan 2026
Viewed by 881
Abstract
Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose [...] Read more.
Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man’s life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa. Full article
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Other

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12 pages, 808 KB  
Systematic Review
Radical Prostatectomy Following Holmium Laser Enucleation of the Prostate (HoLEP): A Systematic Review of Perioperative, Oncological, and Functional Outcomes
by Stamatios Katsimperis, Lazaros Tzelves, Titos Markopoulos, Themistoklis Bellos, Konstantinos Douroumis, Nikolaos Kostakopoulos and Andreas Skolarikos
Cancers 2025, 17(22), 3685; https://doi.org/10.3390/cancers17223685 - 18 Nov 2025
Viewed by 1542
Abstract
Background: The widespread adoption of holmium laser enucleation of the prostate (HoLEP) has led to a growing number of men subsequently diagnosed with localized prostate cancer requiring radical prostatectomy (RP). However, anatomical alterations after HoLEP may increase surgical complexity and affect outcomes. [...] Read more.
Background: The widespread adoption of holmium laser enucleation of the prostate (HoLEP) has led to a growing number of men subsequently diagnosed with localized prostate cancer requiring radical prostatectomy (RP). However, anatomical alterations after HoLEP may increase surgical complexity and affect outcomes. This systematic review aimed to synthesize current evidence on perioperative, oncological, and functional outcomes of RP following HoLEP. Methods: A systematic literature search was conducted in PubMed, CENTRAL, and ClinicalTrials.gov through to September 2025 in accordance with PRISMA 2020 guidelines (PROSPERO CRD420251134483). Eligible studies included patients undergoing RP after HoLEP with reported perioperative, oncologic, or functional data. Methodological quality was assessed using the ROBINS-I tool, and results were synthesized narratively. Results: Eight retrospective studies comprising 202 patients were included. RP after HoLEP was technically feasible across open, laparoscopic, and robotic approaches. Operative time and the need for bladder-neck reconstruction were increased, reflecting post-enucleation fibrosis, but major complication rates (<5%) and blood loss were comparable to primary RP. Oncological outcomes were preserved, with positive surgical margin rates of 6–20% and biochemical recurrence rates of 7–15%, similar to those of primary RP. Functional recovery, particularly urinary continence, was slower initially but generally equivalent at 12 months. Erectile function outcomes were variable but satisfactory when nerve-sparing was feasible. Conclusions: Radical prostatectomy after HoLEP is a technically demanding yet safe procedure that achieves oncologic and long-term functional outcomes comparable to primary prostatectomy. Prior HoLEP should not preclude curative surgical management of prostate cancer, provided the operation is performed by experienced surgeons in high-volume centers. Full article
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